Reprogramming of Prostate Stromal Cells by Prostate Inflammation

前列腺炎症对前列腺基质细胞的重编程

• 批准号: 9247932
• 负责人: Li Xin
• 金额: $ 18.52万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9247932
• 关键词: Acute Prostatitis; Adult; Affect; Applications Grants; Bacteria; Bacterial Infections; Basal Cell; Basement membrane; Biological; Biological Assay; Candidate Disease Gene; Cell Differentiation process; Cell physiology; Cells; Clinical; Complement; Disease; Epithelial Cells; Indolent; Infection; Inflammation; Inflammatory; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of prostate; Mediating; Medical Care Costs; Mesenchymal; Microarray Analysis; Modeling; Molecular; Mus; Natural regeneration; Play; Prognostic Marker; Prostate; Prostatic Neoplasms; Regulation; Role; Signal Transduction; Stromal Cells; Testing; Tissue Microarray; Tumor Cell Invasion; Urogenital Sinus; base; cell type; fetal; genetic approach; improved; mortality; mouse model; novel; prognostic; programs; prostatitis; public health relevance; transcriptome; transcriptome sequencing; tumor

 DESCRIPTION (provided by applicant): Basal and luminal cells are the two major types of epithelial cells in the prostate. These two types of cells are mostly independently sustained in adults and both can serve as the cells of origin for prostate cancer. Recent studies using mouse models revealed that prostate cancer originated from basal epithelial cells are more invasive than those derived from luminal cells. Interestingly, initiation of this invasive type of prostate cancer is limited by a cellular process called basal-to-luminal differentiation. We showed recently that basal-to-luminal differentiation is enhanced in the context of prostatitis induced by infection from uropathogenic bacteria, suggesting that prostate stromal microenvironment substantially impinge on the differentiation program of prostate basal epithelial cells. In this application, we propose to use a combination of molecular biological and genetic approaches to uncover how the bacterial infection induced prostatitis affects prostate stromal cell transcriptome. We seek to identify prostate stromal cell-mediated signaling that plays critical roles in regulation of basal epithelial cell differentiation, and verify whether they serve as prognostic markers for aggressive prostate cancer.

 描述（由适用提供）：基础和腔细胞是前列腺中上皮细胞的两种主要类型。这两种类型的细胞主要在成年人中独立维持，并且都可以用作前列腺癌的原产细胞。使用小鼠模型的最新研究表明，前列腺癌起源于基底上皮细胞比源自腔细胞的癌更具侵入性。有趣的是，这种侵入性的前列腺癌类型的启动受到称为基底至亮露分化的细胞过程的限制。我们最近表明，在由前列腺炎引起的前列腺炎的背景下，基础向淋巴的分化得到了增强 尿道病细菌感染，表明前列腺基质微环境显着影响前列腺碱性上皮细胞的分化程序。在此应用中，我们建议使用分子生物学和遗传方法的组合来揭示细菌感染如何影响前列腺基质细胞转录组。我们试图确定前列腺基质细胞介导的信号传导，该信号在调节基本上皮细胞分化中起着关键作用，并验证它们是否是攻击性前列腺癌的预后标记。